Submissions for variant NM_000255.4(MMUT):c.422C>T (p.Ala141Val)

gnomAD frequency: 0.00001  dbSNP: rs565348836

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001211091	SCV001382613	pathogenic	not provided	2023-09-27	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 141 of the MUT protein (p.Ala141Val). This variant is present in population databases (rs565348836, gnomAD 0.007%). This missense change has been observed in individual(s) with methylmalonic aciduria (PMID: 30209273). ClinVar contains an entry for this variant (Variation ID: 941328). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MUT protein function. This variant disrupts the p.Ala141 amino acid residue in MUT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26454439, 28101778). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV001578678	SCV001805949	uncertain significance	Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	2021-07-14	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001578678	SCV004805725	likely pathogenic	Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	2024-03-29	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001828686	SCV002075437	uncertain significance	Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency	2020-01-20	no assertion criteria provided	clinical testing